The cure rate of malignant tumors is more and more increasing by early diagnosis and progress in therapies, but metastases of malignant tumors are often beyond current therapies and pose one of the important medical problems. At present, chemotherapies are used to arrest metastases following removal of tumors with unsatisfactory results, so that it would be desirable to develop more effective inhibitors against malignant tumor metastases.
Bone tissues are one of the most favored sites of metastases of malignant tumors, as a report shows that bone metastases occurred in about 30% of all the cancer cases from autopsy. Among malignant tumors, cancers of the lung, breast, prostate or the like are particularly known to be likely to metastasize to bone.
Vitamin D compounds are known to show a wide variety of physiological activities such as calcium metabolism regulation, growth inhibition or differentiation-inducing of tumor cells or the like, and immunoregulation. Vitamin D derivatives having an oxygen atom at the 22-position, which are particularly preferred compounds as malignant tumor metastasis inhibitors of the present invention, are known to have very few side effects commonly associated with this type of vitamin D compound. These compounds have been known to induce hypercalcemia, and they have been reported to be effective for psoriasis, secondary hyperparathyroidism or the like (for example, see JP No. 183534A/1988, JP No. 86382/1994, etc.). They are also known to have antitumor effects, but have not been reported yet to show inhibitory effects against metastases of malignant tumors.
It is an object of the present invention to provide metastasis inhibitors, malignant tumors and particularly pharmaceutical agents for inhibiting bone metastases of malignant tumors.